Kaposi’s sarcoma occurring in a glioblastoma multiforme on temozolomide

Dear Editor, Kaposi’s sarcoma (KS), an uncommon tumor, is a known complication among individuals receiving immunosuppressive therapy after organ transplantation and those with acquired immunodeficiency syndrome. Infection with human herpesvirus 8 (HHV8) and cell-mediated immunodeficiency also increase the risk of KS. Temozolomide (TMZ) is primarily used as an alkylating agent for treating primary brain tumors. Here, we present a case of glioblastoma multiforme (GBM) with multiple KS after using TMZ. A 72-year-old male was diagnosed with GBM after experiencing memory impairment and the detection of a 5.5 cm lobulated hypodense mass in the left temporoparietal lobe on a computed tomography (CT) scan. The tumor was surgically resected 2 weeks later, and histology confirmed GBM (glioblastoma WHO grade IV). Neoadjuvant chemotherapy with TMZ was begun with a concomitant therapy phase of at least 42 days, followed by three cycles of the TMZ maintenance phase (5 days for each cycle). During the concomitant phase, TMZ was orally administered at 50–75 mg/m2/day alongside radiotherapy (fractionated focal irradiation given for a total of 54–60 Gy, divided into 30–33 therapy sessions). In the maintenance phase, TMZ was administered at 150 mg/m2/day. Four months later, he was referred for the evaluation of multiple nodular lesions that had recently appeared on his trunk and extremities. Physical examination revealed multiple asymptomatic violaceous round nodules, ranging from 0.5 to 2 cm in diameter, on the eyelids, neck, chest, abdomen, back, and bilateral upper and lower limbs [Figure 1a]. A skin biopsy from one of the nodules on the chest revealed histopathology consistent with KS. Tumor cells expressed CD34, CD31, ERG, and HHV-8 antigens [Figure 1b-d]. Laboratory investigations, including screening for human immunodeficiency virus (HIV), were negative. The patient was found to have normal leukocyte, lymphocyte, and neutrophil, but a profound decrease amount of the CD4 + count of 156 cells/mm3 (normal range: 500–1500 cell/mm3) was noticed. A CT scan of the chest and abdomen showed multiple pulmonary metastases in the bilateral lung and chest wall muscles. Despite discontinuing TMZ, the lesions continued to progress. Subsequently, bevacizumab was initiated at a dosage of 10 mg/day, resulting in stabilization of the lesions and regression of some.Figure 1: (a) Clinical image of multiple 0.5–2 cm, violaceous round nodules on the eyelids, neck, chest, abdomen, back, and bilateral upper and lower limbs. (b) Histopathological image: Skin biopsy specimen from the chest reveals the nodular stage of Kaposi sarcoma (H and E, ×100). (c) Positive ERG immunostain (×200). (d) Human herpesvirus 8 immunopositivity of endothelial cell nuclei (×200).TMZ received its initial approval in 2005 for treating newly diagnosed GBM. The reported dermatologic side effects associated with TMZ are rare, which include urticaria, maculopapular rash, panniculitis, drug reaction with eosinophilia and systemic symptoms, and Steven–Johnson syndrome.[1,2] Out of 300 Korean patients with malignant gliomas who underwent treatment with TMZ, 5.3% experienced a skin rash, with none of the cases classified as severe.[3] Continuous, frequently scheduled administrations of TMZ may carry a higher risk of resulting in isolated and severe lymphocytopenia and reduced CD4+ cell counts, particularly affecting other hematological cell lines to a lesser extent. The specific immunologic mechanisms underlying this immunosuppressive pattern are still unknown. TMZ’s specific influence on lymphocytes may arise from its effects either on the thymus or at a shared lymphoid precursor level. In addition, TMZ is proposed to be selectively transported into CD4+ lymphocytes, inducing cytotoxic effects specifically within the CD4+ compartment.[4] The frequent and prolonged use of corticosteroids additionally exacerbates lymphocytopenia and promotes an immunosuppressive state. The administration of cytotoxic drugs, infections such as HIV and human T-cell lymphotropic virus type I, and idiopathic CD4+ T-lymphocytopenia are possible causes of predominant CD4+ lymphocytopenia that should be excluded.[5] Radiotherapy plays a crucial role in treating KS, serving as the primary treatment for solitary lesions or as palliative therapy for disseminated forms.[5] However, there is one report suggesting an association between radiotherapy and KS, possibly due to its potential to impair local immunosurveillance.[6] The characteristic skin lesions of KS are erythematous to darkish-reddish nodules, and involvement of the oral and genital mucosa is common. Visceral localizations, particularly in the gastrointestinal and respiratory tracts, are also frequently seen. In individuals undergoing immunosuppressive therapy, KS frequently regresses spontaneously following a reduction or discontinuation of the immunosuppressive treatment. There is only one reported case believed to be caused by TMZ, attributed to its CD4 + suppressive effect.[5] KS often regressed after reducing or stopping immunosuppressive therapy in transplant recipients. Localized lesions may be managed with radiotherapy, cryotherapy, or intralesional vinblastine, while systemic treatments such as doxorubicin, paclitaxel, bleomycin, and bevacizumab may be required for extensive skin lesions and symptomatic visceral involvement.[7] In conclusion, we report a patient with multiple KS, which were associated with T-cell-mediated immunodeficiency. In this patient, a significant reduction in CD4+ count was observed, likely resulting from intense and continuous TMZ chemotherapy. Monitoring lymphocyte and CD4+ cell counts can provide valuable insights. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement All data generated or analyzed during this study are included in this published article. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.